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PubMed2026

miRNA Target Prediction: An Overview of the Past and Current Tools.

MicroRNAs (miRNAs) are among the most studied molecules in recent years, and since their discovery, many miRNAs have been identified across various species. As members of the non-coding RNA family, miRNAs are key players in post-transcriptional gene regulation. These molecules can inhibit translation or promote degradation of messenger RNA (mRNA) by binding to the 3' untranslated region (UTR) of mRNA, thereby influencing almost all biological processes. To identify a miRNA's biological role, it is essential to predict the target sites to which it binds, a goal made possible through bioinformatics tools. This chapter discusses the bioinformatics tools commonly used for this purpose. Also, it analyzes the main factors considered in target prediction, such as seed match, free energy, conservation, site accessibility, multiple binding site contribution, and machine learning and deep learning approaches. Understanding the principles underlying these predictive methodologies is crucial for advancing one's biological research on miRNAs.

MicroRNAs↗

PubMed1977

RNA methylation and control of eukaryotic RNA biosynthesis. Effects of cycloleucine, a specific inhibitor of methylation, on ribosomal RNA maturation.

The role of RNA methylation in the control of ribosome production in mammalian cells has been reinvestigated through a study of the effects in vivo of cycloleucine, a specific and reversible inhibitor of nucleic acid methylations. No close coupling is observed between methylation and transcription. During an extensive blocking of methylation, the synthesis of preribosomal 45-S RNA continues, although at a slightly reduced rate. Transcription and methylation can be temporarily uncoupled in vivo without impairing significantly the efficiency of the subsequent maturation of the transcript which takes place when the methylation is resumed. At the post-transcriptional level, two main observations are made. First, the cleavage pattern of ribosomal RNA is not qualitatively modified by the drug treatment. Preribosomal 45-S RNA which is synthesized during an extensive blocking of methylations (95%) is cleaved in vivo in a stepwise fashion into molecules resembling the species of the normal processing. Undermethylation does not result in the appearance of new size products and no extensive or rapid degredation of rRNA precursors can be detected. Second, the global efficiency of the process of ribosomal RNA maturation is severely affected, in quantitative terms; the undermethylation partially inhibits several stages in the maturation pathway and does not block selectively at a definite step of processing, as previously reported by others. Two main modifications are observed. (a) In the nucleus, the life times of the various undermethylated intermediates of ribosomal RNA maturation are markedly increased and a significant accumulation of these forms is detected by long-term labelling studies. (b) The rate of appearance of ribosomal 28-S RNA into the cytoplasm is severely affected (85-90% inhibition), in much higher proportions than the formation of its immediate precursor, nuclear 28-S RNA, thus suggesting a particular sensitivity to a lack of methylation of the last stage of preribosome maturation (possibly the release to cytoplasm). Finally, if a normal level of methylation does not appear to be stringently required for the completion of ribosomal RNA maturation, our results indicate that the degree of RNA methylation can modulate the general efficiency of the maturation processess.

Amino Acids↗

PubMed1976

Androgen receptors and the molecular basis for the action of antiadrogens in the ventral prostate.

In the rat ventral prostate, various antiandrogens can interfere with the normal formation of an androgen-receptor complex which appears to be required for androgen action. Some of the antagonists may act by inhibiting the enzymatic formation of 5 alpha-dihydrotestosterone or by competing with androgens for the binding sites on the receptors, whereby interacting with and altering the receptor molecules themselves. If the action of an androgen-receptor complex can indeed occur at the stage of gene transcription as well as in certain post-transcriptional processes, the molecular site of antiandrogen action may be in the nuclei and/or cytoplasm of the target cells.

Androgen Antagonists↗

PubMed1979

On pre-messenger RNA and transcriptions. A review.

From the present review integrating old and new data emerge a few principles of gene expression in eukaryotes, and an infinite variety of possible mechanistic details generating the overal pattern. The few principles, most of which are not fundamentally new, may thus be summarized. 1) The eukaryotic genome is subdivided into transcriptional units: into transcriptons which are subject to individual activation controlled at DNA level. 2) Viral genomes may contain one or a few transcriptons, while cells of multicellular organisms contain from 3 x 10(3) in diptera up to an estimated 2 x 10(5) in birds and mammals. 3) Transcriptons may include one or several coding sequences. 4) Transcriptons vary considerably in size: in mammals and birds their size spectrum falls into the 2,000 to 20,000 bp range. 5) Units of coding information constituting one message (genes) and, possibly, units of regulative information are frequently broken up and stored within the transcripton in sub-genic blocks (of so far unknown significance) in general located at a certain distance from the 5' and 3' transcript terminals which are determined by the promotor and terminator signals. 6) The gene, in its specific definition as the functional unit underlying the phenotype, is in general constituted posttranscriptionally by the processing mechanisms from the mosaic of its genomic subunits in the transcripton; segments of coding, service and regulative sequences are recombined within themselves and with each other, polygenic transcripts separate into their unit messages. 7) Activated transcriptons produce pre-mRNA; these primary transcripts are colinear with the DNA of the transcriptional unit. 8) Primary pre-mRNA is processed into secondary pre-mRNA's by extragenic cleavage and intragenic ("splicing") processing, giving rise stepwise to functional mRNA. During this process chemical modifications as methylation, 5'-terminal capping and 3'-terminal polyadenylation take place. 9) Translation yields either potentially functional polypeptides or polycistronic polyproteins subject to further processing. 10) Processing is a regulated process; it involves many of the possible phases and mechanisms of post-transcriptional regulation (cf. 39, 40).

Animals↗

PubMed2026

A pan-cancer analysis of MEX3D in human tumors.

BACKGROUND: MEX3D, a member of the MEX3 RNA-binding protein family, has emerged as a potential regulatory molecule in cancer. However, its role across different tumor types remains largely unexplored. METHODS: We conducted a pan-cancer analysis of MEX3D using transcriptomic and proteomic data from the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Clinical Proteomic Tumor Analysis Consortium (CPTAC). Expression patterns, clinical correlations, survival outcomes, genetic alterations, RNA modification associations, immune infiltration, and functional enrichment were systematically evaluated. RESULTS: MEX3D was significantly dysregulated in numerous cancers at both mRNA and protein levels. Its expression correlated with tumor stage in ACC, LIHC, OV, SKCM, and THCA. Elevated MEX3D expression was associated with poor overall survival (OS) and disease-specific survival (DSS) in multiple malignancies, including ACC, LGG, LUAD, and MESO. Genetic alteration analysis revealed frequent amplifications and mutations, particularly in SARC and OV. MEX3D was positively correlated with RNA modification-related genes (m1A, m5C, m6A) and immune regulatory genes such as CD276, TGFB1, VEGFA, and ICOSLG. Additionally, MEX3D expression showed significant associations with tumor mutational burden (TMB), microsatellite instability (MSI), and cancer-associated fibroblast infiltration. Functional enrichment analyses indicated that MEX3D-related genes are involved in reproductive cellular processes, RNA binding, the Hippo signaling pathway, and microRNA-related oncogenic pathways. CONCLUSION: This pan-cancer analysis highlights the heterogeneous expression and cancer-specific prognostic significance of MEX3D. MEX3D is associated with immune infiltration, immune regulatory genes, RNA modification-related genes, TMB/MSI, and pathways involved in gene regulation and tumor progression. These findings suggest that MEX3D may participate in cancer-specific post-transcriptional and microenvironmental regulatory networks.

Biomarker↗

PubMed2025

Dysregulation of miRNAs in Sicilian Patients with Huntington's Disease.

Background/Objectives: Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by a CAG nucleotide repeat expansion in the Huntingtin (HTT) gene. Dysregulation of microRNAs (miRNAs), key post-transcriptional regulators of gene expression, has been implicated in HD pathogenesis, although their specific roles remain incompletely understood. Methods: Peripheral blood mononuclear cells from Sicilian HD patients and matched healthy controls were subjected to small RNA sequencing. Differential expression analysis was conducted using DESeq2 (version 1.44.0), with significance defined as |fold change| ≥ 1.5 and adjusted p ≤ 0.05. Ingenuity Pathway Analysis (IPA) was applied to assess functional enrichment, focusing on neurological diseases, inflammatory processes, and miRNA-RNA messenger (mRNA) interaction networks. Results: A total of 790 differentially expressed miRNAs were identified in HD patients (270 upregulated and 520 downregulated). IPA revealed enrichment in pathways related to organismal injury, neurological disease, and inflammatory responses. Four major regulatory networks linked differentially expressed miRNAs to neurodegenerative processes, with target genes involved in neuroinflammation, cellular stress responses, and metabolic dysfunction. Cross-referencing with previous RNA-seq data identified 5721 high-confidence miRNA-mRNA interactions, implicating 721 target genes across 54 key canonical pathways. Conclusions: HD patients exhibit a distinct and reproducible peripheral blood miRNA expression signature. These dysregulated miRNAs may represent accessible biomarkers and provide mechanistic insights into HD pathogenesis, with potential applications for diagnosis, prognosis, and therapeutic development.

Huntington’s disease↗

PubMed2025

Identification of circulating miRNA alterations in diabetes patients excluding periodontitis effects: insights into target gene downregulation in diabetic complications.

BACKGROUND: Diabetes mellitus (DM) induces systemic complications through chronic metabolic dysregulation. Circulating exosomal microRNAs (miRNAs) are emerging as key regulators of post-transcriptional gene expression and may drive diabetes-associated pathologies. Although miRNAs have been widely studied in diabetes, the characterization of PD-independent miRNA signatures across tissues remains limited. This study aimed to identify DM-specific miRNA alterations and their contribution to systemic metabolic dysfunction independent of PD. METHODS: Exosomes were isolated from plasma samples, and small RNA sequencing was performed to identify differentially expressed miRNAs (DE-miRs) using the limma R package. Predicted target genes were identified using TargetScan and validated through bulk RNA sequencing datasets from four tissues-foot, kidney, pancreas, and retina. Differentially expressed genes (DEGs) were analyzed, followed by Gene Ontology Biological Process (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment to elucidate diabetes-related mechanisms. RESULTS: We identified 9 upregulated and 6 downregulated DE-miRs specific to the diabetic group. TargetScan predicted 216 upregulated and 64 downregulated target genes. Functional validation revealed that these genes were enriched in pathways related to glucose metabolism, cellular stress response, and tissue repair. Notably, SREK1 and GLIPR1 were commonly detected across all four tissues, suggesting potential systemic regulators of diabetes-related complications. CONCLUSION: This study suggests that circulating exosomal miRNAs, independent of periodontitis, may function as systemic regulators in diabetes. Unlike previous studies, which did not distinguish co-morbid periodontitis, we specifically defined PD-independent miRNA signatures and validated their cross-organ regulatory effects on target genes. Our results revealed a cross-organ miRNA-mRNA regulatory network and identified common regulatory targets. These findings provide insights into both systemic and organ-specific mechanisms underlying diabetic complications and highlight the potential of miRNAs as biomarkers and therapeutic targets.

Humans↗

PubMedDate not supplied

[Nuclear RNP, containing pre-mRNA. XIV. Nature of particles, containing 5'- and 3'-end structures].

Some characteristic peculiarities of the 5'-end and 3'-end structures of pre-mRNA isolated from nuclear RNP particles have been investigated: presence of triphosphorylated nucleotides on the 5'-ends, as a characteristic of the primary product of transcription; presence of modified 5'-ends -- blocked and methylated structures -- caps; presence of poly(A) blocks attached to the 3'-end of pre-mRNA during post-transcriptional transformation of the latter. It was shown that pre-mRNA isolated from nuclear RNP particles contained triphosphorylated nucleotides as well as a "cap" structure at the 5'-ends. On the 3'-ends of pre-mRNA from nuclear RNP particles isolated in the presence of a RNAse inhibitor, the presence of poly(A) blocks have been shown. These poly(A) structures are separated very easily from pre-mRNA during mild RNAase digestion. This is the reason why they are not detected in 30S monoparticles, containing pre-mRNA fragments connected with one informofer. Almost all poly(A) complexes in this condition are combined with proteins and have the sedimentation coefficient of about 14S. It was concluded that formation of nuclear pre-mRNA containing RNP-particles take place just after the onset of RNA synthesis. All processing steps occur with pre-mRNA packed in nuclear RNP particles.

Animals↗

PubMed1979

Prolactin-mediated transcriptional and post-transcriptional control of casein gene expression.

The mechanism by which prolactin, a peptide hormone, regulates casein gene expression has been studied in mammary gland organ culture. After prolactin addition, a 2-4 fold increase in the rate of casein mRNA transcription was observed within 1 hr and maintained for at least 24 hr. This increased rate of transcription is not sufficient to account for the mass accumulation of casein mRNA. The half-life of casein mRNA is also increased 17-25 fold in the presence of prolactin. This change in casein mRNA half-life, coupled with a 2-4 fold increase in the rate of transcription, can account for the normal accumulation of casein mRNA observed after prolactin addition. This hormone-induced change in casein mRNA half-life appeared to be selective, since prolactin was found to exert only a slight effect (1-4 fold) on the half-life of poly(A) RNA determined under identical pulse-chase conditions. The hormonal regulation of casein gene expression thus does not app-ar to be an "all or none" process occurring only at the transcriptional or post-transcriptional levels, but rather may involve a coordinated response at several levels to permit the efficient expression of specialized differentiated functions.

Animals↗

PubMed2026

RNA dysregulation as a determinant of aging and neurodegenerative vulnerability.

In the nervous system, aging causes deterioration of cellular and molecular processes that are associated with declines in cognition, sensory perception, and motor coordination. Aging is also the strongest risk factor for neurodegenerative disease, yet the mechanisms by which aging predisposes neurons to dysfunction remain incompletely understood. While genomic instability, proteostasis decline, mitochondrial dysfunction, and chronic inflammation have dominated prevailing models, recent evidence highlights RNA dysregulation as a central component of age-associated decline. In this review, we summarize recent findings suggesting that aging progressively erodes RNA regulatory fidelity through alterations in RNA-binding protein abundance, localization, biophysical behavior, and RNA interactions. We argue that age-dependent RNA dysregulation represents an important mechanism that converges with genetic risk to drive neuronal vulnerability and neurodegeneration.

RNA dysregulation↗

PubMed1977

Post-transcriptional regulation of ribosome accumulation during myoblast differentiation.

The synthesis, accumulation and stability of rRNA were examined in embryonic quail myoblasts differentiating in cell culture. Quail myoblasts initially divide rapidly in culture, and accumulate 28S and 18S rRNA and ribosomes at a rate which maintains a constant ribosome content during cell division. After these myoblasts fuse, cell division ceases and ribosomes accumulate in fibers, but at a reduced rate which is only one fourth that in dividing myoblasts. Measurements of rRNA stability by 3H-methyl-methionine pulse-chase analysis show that 28S and 18S rRNA formed by fibers turn over with half-lives of 45 hr, and rRNA formed by myoblasts remains stable until fusion and then also turns over in fibers. Turnover of rRNA in fibers accounts for only half the reduction in ribosome accumulation following myoblast fusion. Measurements of the incorporation of 3H-adenosine into rRNA and ATP pools show that the rates of synthesis of rRNA precursor do not decrease after myoblast fuse, but half the rRNA molecules synthesized by fibers are degraded during processing. Degradation of rRNA during processing reduces the rate of formation of 28S and 18S rRNA, and together with rRNA turnover quantitatively accounts for the reduced rate of ribosome accumulation in fibers.

Adenosine↗

PubMed1976

Structure, synthesis, and post-transcriptional modification of ribosomal ribonucleic acid in Bdellovibrio bacteriovorus.

The structure, synthesis, and post-transcriptional modifications of 23-S and 16-S ribosomal RNAs (rRNAs) have been studied in the facultatively parasitic bacterium, Bdellovibrio bacteriovorus. The mature 23-S and 16-S type of rRNAs in Bdellovibrio are larger than the analogous molecules in Escherichia coli by at least 1.0 - 10(5) and 0.5 - 10(5) daltons, respectively, and have a conformation different from E. coli rRNAs as judged by relative electrophoretic mobilities in polyacrylamide gels with and without denaturing conditions. Studies on the kinetics of synthesis and maturation of ribosomal RNA in Bdellovibrio show that precursor forms analogous to p23-S and p16-S in E. coli are synthesized. In addition, some earlier precursor rRNAs in Bdellovibrio are seen that appear analogous to the 25S and 17.5-S pre-rRNAs that have only been observed in the RNAase III deficient mutant of E. coli strain AB301-105 (Nikolaev, Birenbaum, M. and Schlessinger, D. (1975) Biocheim, Biophys. Acta 395, 478-489). These early precursor stages have not been observed in other procaryotic species, including E. coli that have normal levels of RNAase III. The results from the Bdellovibrio system provide that the 25-s and 17.5-S pre-rRNAs are normal stages of rRNA modification and are part of a multiple step maturation process, and therefore are not aberrations associated with the RNase III deficient mutation.

Bdellovibrio↗

PubMed2026

Integrated miRNA-mRNA profiling reveals candidate regulatory relationships associated with high-fat diet-induced muscle lipid deposition in black seabream (Acanthopagrus schlegelii).

High-fat diets are increasingly used in aquaculture due to their protein-sparing effects; however, the post-transcriptional regulatory mechanisms of fish muscle in response to high-fat diets (HFD) remain unclear. In this study, juvenile black seabream were fed either a normal-fat diet (NFD) or a HFD to investigate the miRNA-mRNA regulatory network associated with diet-induced muscle lipid deposition. Oil Red O staining and biochemical analysis showed that high-fat diet feeding markedly increased lipid droplet accumulation and crude lipid content in muscle, indicating significant induction of muscle lipid deposition. Integrated mRNA and miRNA expression profiling revealed substantial transcriptomic and post-transcriptional responses to high-fat diet challenge. A total of 271 differentially expressed genes were identified, including 120 upregulated and 151 downregulated genes. Through combined target prediction and expression correlation analysis, thirteen candidate inverse miRNA-mRNA relationships were subsequently identified, and RT-qPCR supported the expression patterns of selected miRNAs and mRNAs. These pairs included miR-499-x-dmgdh, miR-499-y-gatm, miR-727-y-ass1, miR-4649-x-foxo4, miR-9129-z-myl7, and several novel miRNA-mediated interactions involving adk, chst11, lypla2, frem2, kcnc4, wars1, bag2, and capn2. Functional analysis suggested that these regulatory pairs were mainly associated with metabolic adaptation, structural remodeling, and cellular stress responses. In particular, gatm, dmgdh, ass1, and adk were associated with energy metabolism-related processes, including pathways previously linked to Ampk regulation, whereas myl7, frem2, and kcnc4 may contribute to muscle structural maintenance and excitability regulation. Overall, this study provides candidate miRNA-mRNA regulatory relationships potentially involved in high-fat diet-induced muscle lipid deposition and adaptive remodeling in black seabream, offering a basis for future functional studies on muscle metabolism and quality regulation in marine fish.

Animals↗

PubMed2026

Context-dependent roles of DHX9 in Cancer: Molecular mechanisms, biomarker potential, and therapeutic perspectives.

DExH-box helicase 9 (DHX9) is a multifunctional nucleic acid helicase that participates in R-loop homeostasis, genome maintenance, RNA metabolism, and innate immune signaling. Accumulating evidence has linked aberrant DHX9 expression or activity to tumorigenesis, tumor progression, treatment response, and patient prognosis. However, its role in cancer is highly context-dependent, rather than uniformly oncogenic or tumor suppressive. Depending on its molecular partners, subcellular localization, post-translational modifications, tumor genotype, and immune microenvironment, DHX9 may either promote malignant phenotypes or contribute to tumor-restraining processes. In this review, we summarize the molecular characteristics and regulatory properties of DHX9, discuss its roles in genome stability, transcriptional and post-transcriptional control, circular RNA (circRNA) biogenesis, and tumor-immune crosstalk, and evaluate its emerging value as a potential biomarker and therapeutic target. We also highlight key challenges in this field, including mechanistic heterogeneity, insufficient translational validation, and the urgent need for context-informed patient stratification to maximize the clinical utility of DHX9-targeted strategies.

Humans↗

PubMed2025

Oncogenic DEAD-box ATPase DDX41 establishes transcript ensembles via CLK3-dependent and -independent mechanisms.

Post-transcriptional diversification of RNA transcripts mediated by complex processing machinery, including DEAD-box ATPases, establishes and maintains cellular phenotypes. For example, DDX41 controls RNA splicing, innate immune signaling, and genome stability. Although heterozygous DDX41 germline genetic variation occurs in familial myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), the DDX41 contributions to splicing globally, biological processes, and pathogenic mechanisms are incompletely defined. Using a genetic rescue system with Ddx41+/- myeloid progenitors, we established global wildtype DDX41 and pathogenic variant mechanisms. Differing from pathogenic variants of other RNA splicing regulators, DDX41 deficiency compromised multiple splicing steps. DDX41-regulated transcripts encoded factors controlling RNA splicing, including Cdc2-like kinase 3 (CLK3). DDX41 regulated Clk3 transcripts, and elevated CLK3 during myeloid differentiation. Loss-of-function analysis revealed DDX41-regulated splicing commonly, but not always, required CLK3. Thus, through a mechanism utilizing a splicing factor kinase that itself is DDX41-regulated, DDX41 establishes transcript ensembles in myeloid progenitors.

DEAD-box RNA Helicases↗

PubMed2026

EndoV does not measurably affect TadA-dependent A-to-I RNA editing in Escherichia coli under exponential-growth conditions in rich medium.

Adenosine-to-inosine (A-to-I) mRNA editing changes the genetic information post-transcriptionally and was only recently reported to occur in bacteria. Here, we examined whether endonuclease V (EndoV; encoded by nfi) cleaves inosine-containing RNAs in vivo and thereby influences the abundance and fate of A-to-I-edited mRNAs in Escherichia coli. We generated an nfi loss-of-function mutant carrying a premature stop codon and performed RNA sequencing alongside the isogenic wild-type strain. We observed that global and site-specific editing occurrence or levels in both mRNAs and tRNAs were indistinguishable between strains. Moreover, overexpression of EndoV did not affect the number of edited sites, motif enrichment, or editing levels compared with a control strain overexpressing mCherry. Our findings suggest that, in contrast to human EndoV, bacterial EndoV does not regulate the steady-state pool of edited mRNAs in E. coli under nutrient-rich, exponential-growth conditions in vivo.IMPORTANCEAdenosine-to-inosine (A-to-I) mRNA editing is an emerging regulatory layer in bacteria, but the factors that act on edited transcripts are largely unknown. Endonuclease V (EndoV) was a prime candidate because it cleaves inosine-containing nucleic acids and can act on inosine-containing RNA in vitro. By combining loss-of-function and overexpression of EndoV with genome-wide RNA editing measurements, we show that EndoV does not measurably influence TadA-dependent A-to-I mRNA editing in Escherichia coli under standard laboratory conditions. This negative result is important because it rules out a natural effector candidate and redirects attention to other bacterial pathways that may process edited RNAs. Our work, therefore, sharpens mechanistic models for bacterial RNA editing and helps focus future searches for its regulators and physiological roles.

Escherichia coli↗

PubMed2026

Integrated multi-omics analysis reveals a pH-driven metabolic and translational switch in Ureaplasma parvum.

Human ureaplasmas are minimal-genome bacteria and pathobionts of the urogenital tract. They must adapt to fluctuating pH conditions despite the absence of canonical transcriptional regulatory systems. However, the mechanisms underlying these responses remain unclear. This study aimed to construct a system-level model of pH adaptation in this minimal pathogen. We used an integrated multi-omics platform combining proteomics, metabolomics, and RNA modification profiling to construct a system-level model of pH adaptation. The results revealed a bifurcated strategy governed by the differential activation of preexisting, co-regulated functional modules. Under neutral pH conditions (pH 7), Ureaplasma parvum activated energy metabolism and upregulated ATP synthesis while forming a stress-counteracting proteostasis pathway. This may suggest a biological energy state under high stress conditions. Conversely, under acidic stress (pH 5), it activated biosynthesis/translation, showing significant upregulation of ribosomal proteins and accumulation of translation precursors and the polyamine spermidine. This may represent a state of expanded translational capacity. This adaptive switch is accompanied by dynamic reorganization of the epitranscriptome, highlighting the importance of post-transcriptional regulation. This study suggests mechanisms by which minimal organisms achieve adaptive plasticity through sophisticated post-transcriptional and metabolic control, providing a new framework for understanding Ureaplasma physiology and the biology of genome-reduced organisms.IMPORTANCEMinimal bacteria challenge canonical views of cellular regulation. In organisms with radically reduced genomes and sparse transcription factors, how adaptive plasticity is achieved remains a core question. Our study proposes a model in which a simple physicochemical cue-extracellular pH-selects among prewired cellular programs, while post-transcriptional and epitranscriptomic layers fine-tune execution. The findings of this study suggest a multi-omics scheme for how organisms adapt to environmental changes and ensure survival without inducing new circuits or complex transcriptional regulation. Conceptually, it proposes regulation via RNA modifications in processes, such as metabolism, proteostasis, and translation. This framework may be generalizable to other genome-reduced microorganisms. Beyond microbiology, it provides design principles for synthetic biology and offers a mechanistic interpretation of phenotypic tolerance to stress factors. It may encourage the use of pH-linked epitranscriptome signals as measurable indicators of cellular state.

Hydrogen-Ion Concentration↗

PubMed2022

Battle for Metals: Regulatory RNAs at the Front Line.

Metal such as iron, zinc, manganese, and nickel are essential elements for bacteria. These nutrients are required in crucial structural and catalytic roles in biological processes, including precursor biosynthesis, DNA replication, transcription, respiration, and oxidative stress responses. While essential, in excess these nutrients can also be toxic. The immune system leverages both of these facets, to limit bacterial proliferation and combat invaders. Metal binding immune proteins reduce the bioavailability of metals at the infection sites starving intruders, while immune cells intoxicate pathogens by providing metals in excess leading to enzyme mismetallation and/or reactive oxygen species generation. In this dynamic metal environment, maintaining metal homeostasis is a critical process that must be precisely coordinated. To achieve this, bacteria utilize diverse metal uptake and efflux systems controlled by metalloregulatory proteins. Recently, small regulatory RNAs (sRNAs) have been revealed to be critical post-transcriptional regulators, working in conjunction with transcription factors to promote rapid adaptation and to fine-tune bacterial adaptation to metal abundance. In this mini review, we discuss the expanding role for sRNAs in iron homeostasis, but also in orchestrating adaptation to the availability of other metals like manganese and nickel. Furthermore, we describe the sRNA-mediated interdependency between metal homeostasis and oxidative stress responses, and how regulatory networks controlled by sRNAs contribute to survival and virulence.

Bacteria↗